title: Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.
  
  
  OBJECTIVE
  We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.
  
  
  RESULTS
  Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷).
  
  
  CONCLUSIONS
  We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. huaidong.du@ctsu.ox.ac.uk
authors.forename: Huaidong
authors.initials: H
authors.lastname: Du
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Lars
authors.initials: L
authors.lastname: Angquist
authors.forename: Rikke D
authors.initials: RD
authors.lastname: Hansen
authors.forename: Daphne L
authors.initials: DL
authors.lastname: van der A
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Marianne Uhre
authors.initials: MU
authors.lastname: Jakobsen
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Karina
authors.initials: K
authors.lastname: Meidtner
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
mesh_terms: D000328:Adult; D001835:Body Weight / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D015430:Weight Gain / Q000235:genetics; D055815:Young Adult